Dermatophyte-hormone relationships: characterization of progesterone-binding specificity and growth inhibition in the genera Trichophyton and Microsporum

Abstract

We reported previously that Trichophyton mentagrophytes contains a cytoplasmic macromolecule which specifically binds progesterone. Progesterone is also an effective inhibitor of growth of the fungus. We report here studies which characterize more fully the specific binding properties and the functional responses of T. mentagrophytes and taxonomically related fungi to a series of mammalian steroid hormones. Scatchard analysis of [3H]progesterone binding in both the + andmating types of Arthroderma benhamiae and in Microsporum canis revealed a single class of binding sites with approximately the same affinity as that in T. mentagrophytes (Kd, 1 X 10-7 to 2 X 10-7 M). Trichophyton rubrum had a protein with a higher binding affinity (Kd, 1.6 x 10-8 M). Characterization of the [3H]progesterone-binding sites in T. mentagrophytes showed the binder to be a protein which was destroyed by trypsin and heating to 56°C. Previous examination of the steroid-binding specificity in T. mentagrophytes had demonstrated that deoxycorticosterone (DOC) and dihydrotestosterone (DHT) were effective competitors for [3H]progesterone binding. Expansion of this study to include other competitors revealed that R5020 (a synthetic progestin), androstenedione, and dehydroepiandosterone possessed relative binding aflinities which were 20, 11, and 9% of that of progesterone, respectively. Other ligands tested were less effective. Competition studies for the binder in M. canis resulted in similar findings:

Human androgenic steroids affect growth of dermatophytes in vitro

“…Mean thallus diameters in % of control for progesterone [4,5]. However, the hormonal concentrations required to inhibit fungal growth are much higher.…”

Morphological Transition of Paracoccidioides brasiliensis Conidia to Yeast Cells: In Vivo Inhibition in Females

“…A number of hormonal systems in various fungi have been described (10,30). Several fungi have cytosolic proteins that bind mammalian hormones with high affinity and stereospecificity (8,15,30,31).…”

Membrane-bound progesterone receptors coupled to G proteins in the fungus Rhizopus nigricans

“…Some recent studies suggest the association of the mammalian plasma membrane steroid receptors with G proteins [9,10]. In fungi, however, only steroid signaling analogous to the classical mechanism of steroid action has been observed [2,11,12]. In this context we found and partially characterized progesterone receptors in the cytosol from R. nigricans [13].…”

“…It was reported some decades ago that the mammalian gonadal hormones progesterone, 21-hydroxyprogesterone, and dihydrotestosterone inhibit growth of bacteria and some pathogenic fungi [1,2]. In addition to mammalian pathogenic fungi, growth inhibition by mammalian steroids, especially progesterone and 21-hydroxyprogesterone, was observed also in the saprophytic fungus Rhizopus nigricans [3].…”